Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Information Disclosure Statement
The information disclosure statements (IDS) submitted on May 08, 2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Status of Claims
Claims 46-49, 52, 58, 65, 69, 79, 82, 84-85, 133, and 154-167 pending and under examination.
WITHDRAWN REJECTIONS
Claim Rejections - 35 USC § 112
Claims 46-47, 49, 52, 58, 65, 69, 79, 82, 84-85, 133, 154-167 were rejected for reciting a lentivirus-like particle. This rejection is withdrawn due to the general knowledge in the art as well as the paragraph specified by the Applicants in the specification. It is for example, as evidenced by Hyman et al that “Virus-like particle (VLP) is a term that has been in use for about 80 years. Usually, VLP has meant a particle that is like a virus, generally by appearance, but without either proven or actual virus functionality.” (See Hyman et al; Abstract; See PTO-892). It is noted that this term was generally well understood by a person of ordinary skill in the art and is given the general definition of a particle that is like a virus, generally by appearance, but without actual virus genome.
Claims 46-49, 52, 58, 65, 69, 79, 82, 84-85, 133, and 154-167 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement, as they required a lentivirus-like particle, which lacked any description to a lentivirus-like particle, or what constitutes a lentivirus-like particle, any structural or functional features of such particles. The rejection is withdrawn due to the reasons specified above.
MAINTAINED REJECTIONS
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 49, 52, 58, 65, 69, 79, 82, 84-85, 133, and 154-167 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as failing to set forth the subject matter which the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the applicant regards as the invention.
Claims 49, 58, 155, 157-158 and 167 require a biologically active portion of CD24 and other proteins. It is not clear from the specification as to the metes and bounds of the biologically active portion of the various proteins. The specification does not delineate a specific structure or a specific means of identifying the claimed portion of the protein. Further it is unclear as to which activity is envisioned by the claim. It is noted that this rejection is withdrawn for claim 46, 65, 69, 79, 84, 85, 133, 154, 159-166 following cancellation of this term.
Response to Arguments: Applicants argued that the claims have been amended to recite "the Paramyxoviridae envelope protein G or H or the biologically active portion thereof retains fusogenic activity in conjunction with the Paramyxoviridae envelope F protein or the biologically active portion thereof' and that the Paramyxoviridae envelope F protein or a biologically active portion thereof comprises "an N-terminal hydrophobic fusion peptide domain." Applicants indicated that a person of ordinary skill in the art would understand which portions of G/H proteins are necessary for fusogenic cooperation with F proteins and which portions of F proteins mediate membrane fusion. Applicants’ arguments and claim amendments have been reviewed but are not persuasive. It is submitted that the claim does not inform a person of ordinary skill in the art with reasonable clarity regarding what exactly constitutes a biologically active domain. It is submitted that without identifying which amino acids confer the claimed functional features of fusogenic activity or describing any portion that retains fusion peptide domain, a POSA cannot clearly and unequivocally identify which amino acid deletions, truncations, or fragments fall within the scope of the claim. The boundaries of the ”portion” are solely defined by functional result and the specification does not give any structural definition, sequence coordinates or markers to delineate which fragments constitute the claimed portion. As such the claims remain indefinite.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 46-49, 52, 58, 65, 69, 79, 82, 84-85, 133, and 154-167 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement.
The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 46, 49, 58, 65, 69, 79, 84, 85, 133, 154-155, 157-167 require a biologically active portion of CD24 and other proteins. However, the specification lacks any description to what structural features of CD24 or other proteins constitute a biologically active portion of CD24 or any of the other claimed proteins. The specification provides no guidance on how to identify how to measure biological activity of the claimed proteins or how to detect or determine any structural features to identify such biologically active portion of CD24 or any of the other claimed proteins. As such the claim lacks written description to biologically active portion of the claimed proteins in each of the claims.
Claim 48 requires that the fusogen comprises any protein derived from an envelope glycoprotein of any virus of the Paramyxovirus family. Further claim 49 requires that the fusogen pseudotyped with any cell targeting fusion protein comprising a protein derived from any Paramyxoviridae envelope protein G or H and any cell targeting domain. It is noted however that the specification only disclosed amino acid sequences for certain Henipavirus G proteins including Nipah virus, Cedar virus, Mojiang virus and select bat paramyxovirus C protein. However, Paramyxovirus family encompasses multiple genera, including but not limited to Henipavirus, Morbilivirus, Respirovirus, Orthorubulavirus and Avulavirus. The specification does not provide representative features or common structural features covering envelope glycoproteins across full Paramyxoviridae family, nor does it provide guidance demonstrating possession of non-Hepinavirus envelope. Accordingly, it is submitted that the specification fails to provide guidance demonstrating possession of specific non-Hepinavirus envelope glycoproteins. Claims 58, 65, 69, 79, 84, 85, 133, 154-155, and 157-167 inherit these rejections.
Additionally, claims 49 and 167 encompass an enormous genus of compositions that have no support in the specification. The scope of the claim as currently worded encompasses any Paramyxovirus G protein (e.g. Nipah, measles mumps, Sendai etc) any paramyxovirus H protein that are structurally and functionally distinct from G-proteins and any fusion protein comprising biologically active portion of such G or H proteins. As such the specification fails to indicate what is structurally, or functionally a biologically active portion of G or H protein. Further, the fusions can comprise antibodies, peptide ligands, receptor binding domains, growth factors, cytokines, aptamers or any other cell targeting domain. The claim fails to structurally or functionally characterize such cell targeting domains. As such the claim encompasses enormous number of compositions which are structurally distinct. The specification does not disclose any cell targeting protein or targeting domain or any fusion between a Paramyxovirus envelope protein and a targeting domain, any sequence or structure of schematic of such fusion protein. As such it is submitted that the specification does not disclose a representative species of the enormous compositions encompassed by the claim and the specification also does not identify a common structural feature or meaningful guidance allowing a person of ordinary skill in the art to arrive at the claimed compositions. As such the claim lacks written description.
Claims 159-160 require 95% sequence identity to SEQ ID NO: 35-37, and 90% identity to SEQ ID NO: 35-36. Further claim 169 requires 90% sequence identity to SEQ ID NO: 2.
This claimed composition encompasses all compositions comprising >90% identity to SEQ ID NOs: 2, and 35-37. Applicant’s specification only described a polynucleotide comprising SEQ ID NOs: 2, 7 and 35-37. Applicant’s claim encompasses a large number of protein acid sequences. For example, for encompassing all nucleotides comprising >95% identity to SEQ ID NO: 2, there can be up to
32
C
2
×
19
2
=
1.8
×
10
5
different protein sequences, if only substitution variants were considered. It is also noted that the claimed variants encompass deletions and insertions. Applicant’s disclosure does not provide support for all proteins that can result in 95% identity to SEQ ID NOs: 2, and 35-37 to support the instant claims. Nor does the specification provide guidance regarding where the variations are tolerated or not tolerated or any structural guidance or regarding any permissible variants. Thus, Applicants were not in possession of the full scope of the claimed invention at the time of filing of the instant invention.
Claims 155-156 require a Paramyxovirus F protein (155) and for the F protein to be from a Hepinavirus (156). However, the specification does not teach or disclose each and every paramyxovirus F protein as encompassed by the claim. The specification taught the sequence and structure of bat-paramyxovirus F protein. While this demonstrates a single F protein from a bat paramyxovirus, the specification does not provide support for the genus as a whole, which is structurally and functionally diverse. A person or ordinary skill would not conclude that the disclosure reasonably provided support for all paramyxovirus F proteins as claimed. As such the claim lacks written description. Additionally, claim 156 requires the F protein to be from a henipavirus. It is noted that the specification did not demonstrate possession of a Henipavirus F protein. Disclosure of bat paramyxovirus F protein does not demonstrate possession of all Henipavirus F proteins as the two are distinct and unpredictable in sequence, structure and function. As such there is no written description for the scope of the claim in the specification.
Response to Arguments: Applicants argued that the claims have been amended with description of the Paramyxoviridae family G, H, and F proteins, and the specification provides adequate guidance on how to identify the biologically active portion of and the G, H, and F viral proteins, thereby demonstrating possession. Applicant’s arguments are not persuasive.
The specification discloses full-length CD24 and CD47 proteins incorporated into lentiviral particles and evaluated for functional effects on macrophage phagocytosis. There is no disclosure of any structurally defined or experimentally mapped biologically active portions of all Paramyxoviridae G/H/F proteins, nor does the specification provide representative number of such fragments or a structural framework by which a skilled artisan would understand the scope of the claimed genus of biologically active portions. Accordingly, the specification does not demonstrate possession of the full scope of the claimed subject matter.
Applicants argued that “Paramyxovirus envelope glycoproteins, including attachment proteins (G/H) and fusion proteins (F), were well known in the art prior to the filing date, including their structure, function, and use in mediating membrane fusion and viral entry. The present specification does not purport to invent this class of fusogens, but instead incorporates this established class into pseudotyped lentiviral particles having the recited features.” Applicants’ arguments are not persuasive.
Claims 48 and 49 encompass excessively broad species such as G, H, HN and F proteins as well as numerous engineered derivatives, across numerous Paramyxovirus genera (Nipah, Measles, Murine respirovirus, Newcastle disease virus, among many others). In Examples 1-5 the specification provided support for specific lentiviral particles incorporating CD24 and/or CD47, including particular pseudotyped constructs and selected paramyxovirus-derived fusogens such as Nipah virus glycoproteins. However, the claims are not limited to the disclosed embodiments, but instead encompass broad genera of compositions including proteins derived from any Paramyxovirus envelope G, H or F protein as well as any biologically active portion thereof, linked to any cell-targeting domain. Although the specification may disclose certain Henipavirus related glycoproteins, Paramyxovirus family encompasses numerous structurally diverse and functionally distinct genera beyond those described in the specification.
Applicants’ arguments regarding demonstration of possession over the recited scope of sequences, as amended, particularly in view of the guidance in the specification and knowledge in the art relating to permissible variants of such proteins is not persuasive by disclosure of only one variant for a genus encompassing over
1.8
×
10
5
different protein sequences.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 46, 69, 82, 84-85, and 133 are rejected under 35 U.S.C. 103 as being unpatentable over Discher et al (US9050269B2; Published June 09, 2016; hereinafter “Discher”; See IDS filed Oct 10, 2022) in view of Barkal et al (Nature; Published July 21, 2019; Hereinafter "Barkal"; See IDS filed Oct 10, 2022) further as evidenced by Desrosiers et al (Annu. Rev. Immunol. 1990; Hereinafter "Desrosiers"; See PTO-892) and Sanders (Curr Opin Biotechnol. 2002 Oct; See PTO-892).
Regarding claim 46: Discher is directed to a viral particle comprising at least a biologically active portion of CD47. (See Discher Abstract). Discher taught that “Other viruses that are useful to generate the viral particle of the invention include” among other examples simian immunodeficiency virus coated with the envelope proteins, G-protein, from vesicular stomatitis virus (VSV G-pseudotyped). (See Discher, col. 10, lines 30-35). As evidenced by Desrosiers, simian immunodeficiency virus is a lentivirus (See Desrosiers p. 557, 1st para). Discher also taught that “surface marker, for example, CD47, for the purpose of disguising foreign particles thereby disabling macrophage engulfment of the viral particle.” (See Discher, col. 7, lines 35-40). Figure 6 of Discher taught that human-CD47 is sufficient to inhibit phagocytosis. Discher also taught “expressing at least one peptide including at least a biologically active portion of CD47 in a viral particle and administering the viral particle having CD47 expressed to a mammal.” (See Discher, Abstract). Discher did not teach a pseudotyped lentivirus comprising CD24 as required by the claim. However, Barkal taught that CD24 as a highly expressed, anti-phagocytic signal in several cancers and demonstrate the therapeutic potential for CD24 blockade in cancer immunotherapy, (See Barkal Abstract). Barkal taught that CD24 is a potent anti-phagocytic, “don’t eat me” signal that is capable of directly protecting cancer cells from attack by Siglec-10-expressing macrophages. (See Barkal, p. 5, col. 1, last paragraph).
Both Discher and Barkal indicated use of “don’t eat me ligands” to inhibit phagocytic engulfment. At the time of the invention, the art had identified limited number of “don’t eat me” signal elicitors.
As such it would have been prima facie obvious to one having ordinary skill in the art at the time of filing the invention to substitute CD24 for the CD47, especially since both molecules are thought to evoke anti-phagocytic responses and help in evasion of immune response and extending the half-life of the lentiviral particle as taught by Discher. One of ordinary skill in the art would recognize substituting CD27 for CD47 as simply substituting one type of immune evasion molecule for another useful for the same purpose, with a reasonable expectation of success ((KSR Int’l Co. v. Teleflex, Inc., 550 U.S. 398 (2007) pg 14 and 12).
Regarding claim 69: Barkal taught that CD24 and CD47 act in a cooperative manner to block phagocytosis. (See Barkal p. 2, col. 1, para 1). As such one of ordinary skill in the art would be motivated to use CD24 and CD47 to escape phagocytosis of a viral particle.
Regarding claim 82: Discher taught a method comprising administering the viral particles comprising CD24 carrying an effective amount of a therapeutic compound. (See Discher Abstract). Discher also taught gene therapy as a treatment. (See Discher col. 14, lines 65-67). As such it would have been obvious to one of ordinary skill in the art to arrive at a composition recited in claim 82 in view of the teachings of Discher for the reasons mentioned above.
Regarding claims 84 and 85: Figures 8a and 8b of Barkal taught augmented phagocytosis in CD24-deficient tumors compared to wild-type tumors expressing CD24. (See Barkal, p. 4, col. 1, para 1). As such a person of ordinary skill in the art would expect reduced phagocytosis with a lentivirus particle comprising CD24 compared to a lentivirus particle without CD24 in view of teachings of Barkal. Similarly, due to reduced phagocytosis, one of ordinary skill would expect longer half-life as required by claim 85.
Regarding claim 133: Discher taught expression of at least one peptide including at least a biologically active portion of CD47 in a viral particle. As such Discher taught a viral vector comprising nucleic acid encoding CD47. It is also known that the pseudotyped virus comprises viral nucleic acid, as evidenced by Sanders (See Sanders, p. 437, col. 1, para 1). Additionally, for the reasons indicated above, it would have been obvious for a person to express CD24 instead of CD47.
Claims 47-49, 52, 58, 154-159, and 165-167 are rejected under 35 U.S.C. 103 as being unpatentable over Discher et al (US9050269B2; Published June 09, 2016; hereinafter “Discher”; See IDS filed Oct 10, 2022) in view of Barkal et al (Nature; Published July 21, 2019; Hereinafter "Barkal"; See IDS filed Oct 10, 2022) as applied to claims 46, 69, 82, 84-85, and 133 above, further in view of Fejoz et al (WO2017182585A1; Published Oct 26, 2017; Hereinafter "Fejoz"; See IDS filed Oct 10, 2022) further as evidenced by Desrosiers et al (Annu. Rev. Immunol. 1990; Hereinafter "Desrosiers"; See PTO-892), and Sanders (Curr Opin Biotechnol. 2002 Oct; See PTO-892)
Regarding claims 47-48: The teachings of Discher in view of Barkal as evidenced by Desrosiers, and Sanders are set forth above. However, none of the references taught use of a fusogen. However, Fejoz taught a pseudotyped retrovirus-like particle or retroviral vector comprising two types of fusion proteins (also call fusogens): one cell targeting fusion protein and one modulating fusion protein derived from Paramyxoviridae family glycoproteins. (See Fejoz claim 1). It would have been obvious for a person of ordinary skill in the art to use a fusogen or viral fusion proteins for pseudotyping lentivirus for generation of a viral particle as taught by Fejoz.
Regarding claims 49, 154 and 167: Fejoz taught a pseudotyped retrovirus-like particle comprising cell targeting fusion protein comprising a protein derived from an envelope glycoprotein G or H of a virus of the Paramyxoviridae family and glycoprotein derived from an envelope glycoprotein F of a virus of the Paramyxoviridae family (See Fejoz claim 4)
Regarding claims 52 and 156: Fejoz taught a Paramyxoviridae family is preferably a virus of the Morbillivirus genus or of the Henipavirus genus. (See Fejoz, p. 7, lines 35-37). Fejoz taught that the preferred virus of the Henipavirus genus is a Nipah virus (NiV). (See Fejoz, p.8, lines 20-25).
Regarding claims 58 and 155: Fejoz taught that the modified enveloped glycoproteins are derived from the envelope glycoprotein H and the glycoprotein F of a measles virus or from the envelope glycoprotein G and the glycoprotein F of a Nipah virus. (See Fejoz, p.8, lines 25-30).
Regarding claim 157-158: Fejoz taught a glycoprotein NiV-G comprises or consists of the point mutations E501 A, W504A, Q530A and E533A, thus leading to the inability to bind Ephrin-B2 receptor and Ephrin-B3 NiV receptor. (See Fejoz, p.11, lines 30-35)
Regarding claim 159: Fejoz taught a nucleic acid sequence encoding a cell targeting fusion protein derived from an envelope glycoprotein G of a virus of the Paramyxoviridae family wherein the nucleic acid comprises or consists of a SEQ ID NO: 6. SEQ ID NO: 6 is 100% identical to instant SEQ ID NO: 35 (See alignment below). (See Fejoz, p.24, lines 15-20)
Fejoz also taught a pseudotyped retrovirus-like particle or retroviral vector comprising a glycoprotein derived from an envelope glycoprotein F of a virus of the Paramyxoviridae family wherein the glycoprotein F comprises or consists of sequence SEQ ID NO: 16. SEQ ID NO: 16 is 100% identical to instant SEQ ID NO: 37 (See alignment below). (See Fejoz, p.41, lines 1-5)
Query Match 100.0%; Score 2990; Length 736;
Best Local Similarity 100.0%;
Matches 569; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MKKINEGLLDSKILSAFNTVIALLGSIVIIVMNIMIIQNYTRSTDNQAVIKDALQGIQQQ 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MKKINEGLLDSKILSAFNTVIALLGSIVIIVMNIMIIQNYTRSTDNQAVIKDALQGIQQQ 60
Qy 61 IKGLADKIGTEIGPKVSLIDTSSTITIPANIGLLGSKISQSTASINENVNEKCKFTLPPL 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 IKGLADKIGTEIGPKVSLIDTSSTITIPANIGLLGSKISQSTASINENVNEKCKFTLPPL 120
Qy 121 KIHECNISCPNPLPFREYRPQTEGVSNLVGLPNNICLQKTSNQILKPKLISYTLPVVGQS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 KIHECNISCPNPLPFREYRPQTEGVSNLVGLPNNICLQKTSNQILKPKLISYTLPVVGQS 180
Qy 181 GTCITDPLLAMDEGYFAYSHLERIGSCSRGVSKQRIIGVGEVLDRGDEVPSLFMTNVWTP 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GTCITDPLLAMDEGYFAYSHLERIGSCSRGVSKQRIIGVGEVLDRGDEVPSLFMTNVWTP 240
Qy 241 PNPNTVYHCSAVYNNEFYYVLCAVSTVGDPILNSTYWSGSLMMTRLAVKPKSNGGGYNQH 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PNPNTVYHCSAVYNNEFYYVLCAVSTVGDPILNSTYWSGSLMMTRLAVKPKSNGGGYNQH 300
Qy 301 QLALRSIEKGRYDKVMPYGPSGIKQGDTLYFPAVGFLVRTEFKYNDSNCPITKCQYSKPE 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 QLALRSIEKGRYDKVMPYGPSGIKQGDTLYFPAVGFLVRTEFKYNDSNCPITKCQYSKPE 360
Qy 361 NCRLSMGIRPNSHYILRSGLLKYNLSDGENPKVVFIEISDQRLSIGSPSKIYDSLGQPVF 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 NCRLSMGIRPNSHYILRSGLLKYNLSDGENPKVVFIEISDQRLSIGSPSKIYDSLGQPVF 420
Qy 421 YQASFSWDTMIKFGDVLTVNPLVVNWRNNTVISRPGQSQCPRFNTCPAICAEGVYNDAFL 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 YQASFSWDTMIKFGDVLTVNPLVVNWRNNTVISRPGQSQCPRFNTCPAICAEGVYNDAFL 480
Qy 481 IDRINWISAGVFLDSNATAANPVFTVFKDNEILYRAQLASEDTNAQKTITNCFLLKNKIW 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 IDRINWISAGVFLDSNATAANPVFTVFKDNEILYRAQLASEDTNAQKTITNCFLLKNKIW 540
Qy 541 CISLVEIYDTGDNVIRPKLFAVKIPEQCT 569
|||||||||||||||||||||||||||||
Db 541 CISLVEIYDTGDNVIRPKLFAVKIPEQCT 569
Sequence alignment of SEQ ID NO: 35 of instant application to SEQ ID NO: 6 of Fejoz
Query Match 100.0%; Score 2630; Length 524;
Best Local Similarity 100.0%;
Matches 524; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MVVILDKRCYCNLLILILMISECSVGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MVVILDKRCYCNLLILILMISECSVGILHYEKLSKIGLVKGVTRKYKIKSNPLTKDIVIK 60
Qy 61 MIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDLVGDVRLAGVIMAGVAI 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 MIPNVSNMSQCTGSVMENYKTRLNGILTPIKGALEIYKNNTHDLVGDVRLAGVIMAGVAI 120
Qy 121 GIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVLTALQDYIN 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GIATAAQITAGVALYEAMKNADNINKLKSSIESTNEAVVKLQETAEKTVYVLTALQDYIN 180
Qy 181 TNLVPTIDKISCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYE 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 TNLVPTIDKISCKQTELSLDLALSKYLSDLLFVFGPNLQDPVSNSMTIQAISQAFGGNYE 240
Qy 241 TLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVS 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 TLLRTLGYATEDFDDLLESDSITGQIIYVDLSSYYIIVRVYFPILTEIQQAYIQELLPVS 300
Qy 301 FNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGST 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 FNNDNSEWISIVPNFILVRNTLISNIEIGFCLITKRSVICNQDYATPMTNNMRECLTGST 360
Qy 361 EKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTA 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 EKCPRELVVSSHVPRFALSNGVLFANCISVTCQCQTTGRAISQSGEQTLLMIDNTTCPTA 420
Qy 421 VLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRL 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 VLGNVIISLGKYLGSVNYNSEGIAIGPPVFTDKVDISSQISSMNQSLQQSKDYIKEAQRL 480
Qy 481 LDTVNPSLISMLSMIILYVLSIASLCIGLITFISFIIVEKKRNT 524
||||||||||||||||||||||||||||||||||||||||||||
Db 481 LDTVNPSLISMLSMIILYVLSIASLCIGLITFISFIIVEKKRNT 524
Sequence alignment of SEQ ID NO: 37 of instant application to SEQ ID NO: 16 of Fejoz
Regarding claim 165: Discher taught that the “portion of CD47 includes at least a portion of the extracellular domain that interacts with SIRPα.” (See Discher, col. 13, lines 35-40)
Regarding claim 166: Discher taught that the extracellular domain of CD47 comprises SEQ ID NO: 2 which has a portion 100% identical to the claimed SEQ ID NO: 7. (See Discher, col. 13, lines 55-65). See Alignment below.
Query 1 QLLFNKTKSVEFTFCNDTVVIPCFVTNMEAQNTTEVYVKWKFKGRDIYTFDGALNKSTVP 60
QLLFNKTKSVEFTFCNDTVVIPCFVTNMEAQNTTEVYVKWKFKGRDIYTFDGALNKSTVP
Sbjct 19 QLLFNKTKSVEFTFCNDTVVIPCFVTNMEAQNTTEVYVKWKFKGRDIYTFDGALNKSTVP 78
Query 61 TDFSSAKIEVSQLLKGDASLKMDKSDAVSHTGNYTCEVTELTREGETIIELKYRVVSWFS 120
TDFSSAKIEVSQLLKGDASLKMDKSDAVSHTGNYTCEVTELTREGETIIELKYRVVSWFS
Sbjct 79 TDFSSAKIEVSQLLKGDASLKMDKSDAVSHTGNYTCEVTELTREGETIIELKYRVVSWFS 138
Query 121 PN 122
PN
Sbjct 139 PN 140
Alignment of SEQ ID NO: 2 of Discher to SEQ ID NO: 7 of instant application.
Claims 65 and 163-164 are rejected under 35 U.S.C. 103 as being unpatentable over Discher et al (US9050269B2; Published June 09, 2016; hereinafter “Discher”; See IDS filed Oct 10, 2022) in view of Barkal et al (Nature; Published July 21, 2019; Hereinafter "Barkal"; See IDS filed Oct 10, 2022) further as evidenced by Desrosiers et al (Annu. Rev. Immunol. 1990; Hereinafter "Desrosiers"; See PTO-892), and Sanders (Curr Opin Biotechnol. 2002 Oct; See PTO-892) as applied to claims 46, 69, 82, 84-85, and 133 above, further in view of Bleckmann et al (Biol Chem. 2009 Jul; Hereinafter "Bleckmann;" See PTO-892).
Regarding claim 65 and 163-164: The teachings of Discher in view of Barkal as evidenced by Desrosiers, and Sanders are set forth above. However, none of the references taught use of a sialylated CD24. It is noted that Barkal taught that the CD24 sialylation is not necessary for inhibition of phagocytosis by CD24. However, Bleckmann taught that CD24 is naturally sialylated. (See Bleckmann Abstract). Bleckmann also taught that a 2,3-linked sialic acid is present on O-glycans of CD24 as required by claim 164. As such in view of the teachings of Barkal, and Bleckmann, it would have been obvious to use the naturally occurring form of CD24 for inhibition of phagocytosis.
Claims 79 and 162 are rejected under 35 U.S.C. 103 as being unpatentable over Discher et al (US9050269B2; Published June 09, 2016; hereinafter “Discher”; See IDS filed Oct 10, 2022) in view of Barkal et al (Nature; Published July 21, 2019; Hereinafter "Barkal"; See IDS filed Oct 10, 2022) further as evidenced by Desrosiers et al (Annu. Rev. Immunol. 1990; Hereinafter "Desrosiers"; See PTO-892), and Sanders (Curr Opin Biotechnol. 2002 Oct; See PTO-892) as applied to claims 46, 69, 82, 84-85, and 133 above, further in view of Metzner et al (FASEB J. 2008 Aug; Hereinafter "Metzner;" See PTO-892).
Regarding claim 79 and 162: The teachings of Discher in view of Barkal as evidenced by Desrosiers, and Sanders are set forth above. However, none of the references taught the CD47 is displayed on surface of the membrane via a GPI membrane anchor. Metzner taught that RV particles can accommodate GPI-linked proteins. (See Metzner, p. 2735, col. 1, para 1) and that exogenously added recombinant CD59his associates with concentrated RV and LV particles (See Metzner, p. 2736, col. 2, last para). Metzner also taught that GPI anchors for modification of proteins are advantageous in that the amino acid sequence of the mature protein is not altered, increasing the possibility for functionally intact proteins. (See Metzner, p. 2738, col. 2, para 2). As such one of ordinary skill in the art would be motivated to use a GPI anchor for surface modification, absent unexpected results of use of such anchor. It is noted that Discher taught that “a partial protein or peptide fragment, a transmembrane domain or other membrane-anchoring functional domain may be fused to the biologically active CD47 protein fragment, such that the final recombinant protein effectively anchors into the viral particle envelope.” (See Discher, col 13 lines 60-67, col. 14 lines 1-10). As such Discher and Metzner would have provided motivation for a person of ordinary skill in the art to use a membrane anchoring domain to anchor CD47 or CD24 into the viral envelope.
Claims 160-161 are rejected under 35 U.S.C. 103 as being unpatentable over Discher et al (US9050269B2; Published June 09, 2016; hereinafter “Discher”; See IDS filed Oct 10, 2022) in view of Barkal et al (Nature; Published July 21, 2019; Hereinafter "Barkal"; See IDS filed Oct 10, 2022) further as evidenced by Desrosiers et al (Annu. Rev. Immunol. 1990; Hereinafter "Desrosiers"; See PTO-892), and Sanders (Curr Opin Biotechnol. 2002 Oct; See PTO-892) as applied to claims 46, 69, 82, 84-85, and 133 above, further in view of Bai et al (WO2016073704A1; Published May 12, 2016; hereinafter “Bai” See PTO-892).
Regarding claim 160-161: The teachings of Discher in view of Barkal as evidenced by Desrosiers and Sanders are set forth above. However, none of the references taught the sequence of CD24 as required by the claims. The extracellular domain of CD24 is known to comprise the sequence as described in SEQ ID NO: 2. For example, Bai taught an extracellular domain of CD24 comprising the SEQ ID NO: 2 as instantly claimed.
Query Match 100.0%; Score 157; Length 54;
Best Local Similarity 100.0%;
Matches 32; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 SETTTGTSSNSSQSTSNSGLAPNPTNATTKAA 32
||||||||||||||||||||||||||||||||
Db 1 SETTTGTSSNSSQSTSNSGLAPNPTNATTKAA 32
Sequence alignment of SEQ ID NO: 2 of instant application to SEQ ID NO: 62 of Bai
Response to Arguments:
Applicant argued that there is no motivation to substitute the CD47 and additionally, Applicants noted that instant application mentions that “CD47 may not always be completely satisfactory or sufficient to reduce phagocytosis. It has been shown that blockade of CD24 can result in a greater ability to induce phagocytosis than blockade of CD47 in certain cell types, which indicates superior activity of CD24 in certain contexts (Barkal et al. 2019 Nature, 572:392-396).” (See Specification [0073]). Applicant’s arguments that a POSA would lack motivation to substitute CD24 for CD47 are not persuasive, especially in view of Applicants own disclosure. As discussed above, Barkal taught that CD24 functions as an antiphagocytic “don’t eat me” signal capable of reducing macrophage-mediated engulfment. Further as pointed out above, Applicant’s disclosure recognizes CD24 and CD47 as alternative or even preferable immune evasion ligands directed to the same general purpose of reducing phagocytic clearance in view of teachings of Barkal. Accordingly, Applicants own specification further supports the conclusion that one of ordinary skill in the art would have been motivated to substitute CD24 for CD47-containing viral particles taught by Discher in order to achieve the predictable result of reducing macrophage uptake and prolonging particle persistence. Further as previously pointed out, Khalaji et al, taught that there were a limited number of don’t eat me signals known such as SIRPα-CD47 axis, PDL1-PDI axis, MHC1-LILRB1 axis or CD24-Singlec-10 axis. Where the prior art identified finite number of identified predictable solutions for achieving a known purpose, substitution of one known element for another is indicative of obviousness under KSR.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/JAGAMYA NMN VIJAYARAGHAVAN/ Examiner, Art Unit 1633
/EVELYN Y PYLA/Primary Examiner, Art Unit 1633
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